Helminthiasis is a widespread disease found in many animals and is responsible for significant economic losses throughout the world. Among the helminths most frequently encountered are the group of worms referred to as nematodes. The nematodes are found in the gastrointestinal tract, heart, lungs, blood vessels and other body tissues of animals and are a primary cause of anemia, weight loss and malnutrition in the infected animals. They do serious damage to the walls and tissue of the organs in which they reside and, if left untreated, may result in death to the infected animals.
The nematodes most commonly found to be the infecting agents of ruminants include Haemonchus and Ostertagia generally found in the abomasum; Cooperia, Trichostrongylus and Nematodirus generally found in the intestinal tract, and Dictyocaulus found in the lungs. In non-ruminant animals important nematodes include Toxocara and Ancylostoma in the intestine and Dirofilaria in the heart of dogs and cats; Ascaridae in the intestine of swine; and large and small strongyles in equines.
Arthropod ectoparasites commonly infecting warm-blooded animals include ticks, mites, lice, fleas, blowfly, the ectoparasite Lucilia sp. of sheep, biting insects and migrating dipterous larvae such as Hypoderma sp. in cattle, Gastrophilus in horses and Cuterebra sp. in rodents.
Macrolide compounds such as LL-F28249xcex1-xcex compounds, 23-oxo or 23-imino derivatives of LL-F28249xcex1-xcex compounds, milbemycin compounds, avermectin compounds, and mixtures thereof are useful for the prevention and control of helminthiasis and infection by acarids and arthropod endo- and ectoparasites in warm-blooded animals. Parenteral injection of compositions is one of the preferred methods for administering those compounds.
To provide prolonged protection from helminth, acarid or arthropod endo- or ectoparasitic infection or infestation in warm-blooded animals it is desirable to use sustained-release injectable compositions having a relatively high loading of macrolide compounds. However, it is difficult to formulate injectable compositions containing a relatively high loading of macrolide compounds because macrolide compounds are, in general, poorly soluble in conventional solvents used in injectable compositions.
Injectable compositions containing macrolide compounds, vegetable oils and alcohols are described in WO 97/11709. However, that reference discloses that the macrolide compounds may be present in injectable compositions in an amount of only from 0.5% to 5% by weight.
South African Patent Application No. 9708352 discloses injectable macrolide compositions containing macrolide compounds; sesame oil; medium-chain triglycerides or glycol esters or fatty acid esters; and aliphatic or aromatic mono- or polyhydric alcohols and their derivatives or castor oil. However, the injectable compositions described in this reference contain only from 0.2% to 5% w/v of the macrolide compounds.
It is an object of the present invention to provide a sustained-release composition for parenteral administration which comprises a relatively high loading of macrolide compounds.
It is also an object of the present invention to provide a method for preventing or treating helminth, acarid or arthropod endo- or ectoparasitic infection or infestation in warm-blooded animals for prolonged periods of time.
It is another object of this invention to reduce or control the proliferation of helminths, nematodes and parasites in warm blooded animals for prolonged periods of time.
These and other objects of the present invention will become more apparent from the description thereof set forth below and the appended claims.
The present invention provides sustained-release compositions for parenteral administration which comprise on a weight to volume basis: about 5% to 30% of a macrolide compound or mixture of macrolide compounds; about 1% to 10% of a low-HLB surfactant or mixture of low-HLB surfactants; about 1% to 20% of a co-solvent selected from the group consisting of an aromatic alcohol, a cyclic amide and mixtures thereof; and a solvent selected from the group consisting of triglycerides of medium chain fatty acids, glycol esters of medium chain fatty acids and mixtures thereof.
The present invention further provides a method for preventing or treating helminth, acarid or arthropod endo- or ectoparasitic infection or infestation in a warm-blooded animal which method comprises parenterally administering to the animal an anthelmintically, acaricidally or arthropod endo- or ectoparasiticidally effective amount of the composition of this invention.